PROJECT SUMMARY Obesity is a serious public health problem, and a majority of Americans are either overweight or obese. Lifestyle modification, including reduction of energy intake (EI) and increase in energy expenditure (EE) are the cornerstones in the treatment of obesity. Although caloric restriction is the most common dietary strategy used to treat obesity, long-term adherence to caloric restriction is low and weight regain is common. Given the limited success of current options in obesity treatment, there is a critical need for well-designed clinical trials of alternative dietary approaches. Time restricted feeding (TRF) is one such strategy that may increase adherence to caloric restriction and increase weight loss. Recent evidence suggests that a number of metabolic systems are entrained to circadian rhythms, including hormone, lipid and glucose concentrations, intestinal lipid absorption, and autonomic nervous system activity. Restriction of EI to a window of time and, by necessity, the extension of the fasting period may alter diurnal patterns and circadian rhythms in glucose and lipid metabolism in a manner that favors decreased obesity risk. The overall objective of this proposal is to provide a foundation to inform the design of a future large-scale trial to evaluate the efficacy of TRF in generating long-term weight loss. Our overall hypothesis is that a 12-month behavioral weight loss program using TRF in the context of a reduced calorie diet (RCD+TRF) will produce greater weight loss as compared to a behavioral weight loss program using a standard reduced calorie diet (RCD) without time restriction. In this 12-month pilot and feasibility study, 40 overweight and obese individuals will be randomized 1:1 to RCD+TRF (10h self-selected feeding window ending no later than 4 hours prior to their usual bedtime) or a standard RCD (no restriction on feeding duration). Measures include body weight and body composition, energy intake (EI), physical activity (PA), glucose variability, sleep, compliance with caloric and time restriction, and feasibility/acceptability. The specific aims are to: 1) Assess processes critical for the success of a large-scale trial comparing the efficacy of RCD+TRF vs standard RCD on weight loss, EI, PA, sleep, and glucose variability; 2) Assess the safety, tolerability, and acceptability of the RCD+TRF program; 3) Perform preliminary efficacy testing and determine the variability of major outcome measures. Changes in weight, body composition, PA, glucose variability and sleep will be compared between groups to provide preliminary efficacy data and to obtain estimates of variability and effect size to assist with power and sample size calculations for the future large-scale trial. We will also review program attendance, weight loss efficacy, and obtain participant feedback on the RCD+TRF program. These data will be used to optimize the RCD+TRF program prior to the future large-scale trial. Developing novel dietary approaches to promote weight loss and maintenance, and to better allow for individualized care, has the potential for significant public health benefit.